Abstract
BackgroundOptimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. The metabolism of cells and tissues is severely disturbed during asphyxia and resuscitation, and metabolomic analyses provide a snapshot of many small molecular weight metabolites in body fluids or tissues. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis.MethodsA total of 125 newborn Noroc pigs were anesthetized, mechanically ventilated and inflicted progressive asphyxia until asystole. Pigs were randomized to resuscitation with a FiO2 0.21 or 1.0, different duration of ventilation before initiation of chest compressions (CC), and different CC to ventilation ratios. Plasma and urine samples were obtained at baseline, and 2 h and 4 h after return of spontaneous circulation (ROSC, heart rate > = 100 bpm). Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy.ResultsPlasma and urine showed severe metabolic alterations consistent with hypoxia and acidosis 2 h and 4 h after ROSC. Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival.ConclusionsMetabolic profiles of asphyxiated newborn pigs showed severe metabolic alterations. Consistent with previously published reports, we found no evidence of differences between established and alternative resuscitation protocols. Lactate and pyruvate may have a prognostic value, but have to be independently confirmed.
Highlights
Perinatal asphyxia is one of the leading causes of morbidity and mortality in the neonatal period [1] and prompt and effective resuscitation is required to prevent neurological damage
Metabolomics profiles of the samples were analyzed by nuclear magnetic resonance spectroscopy
Baseline plasma hypoxanthine and lipoprotein concentrations were inversely correlated to the duration of hypoxia sustained before asystole occurred, but there was no evidence for a differential metabolic response to the different resuscitation protocols or in terms of survival
Summary
Perinatal asphyxia is one of the leading causes of morbidity and mortality in the neonatal period [1] and prompt and effective resuscitation is required to prevent neurological damage. Key parameters in neonatal resuscitation, such as whether to ventilate with air or pure oxygen during chest compressions (CC), the duration of initial assisted ventilation before initiation of chest CC, or the CC: ventilation (C:V) ratio have not been thoroughly studied. Air was as effective as pure oxygen in resuscitation from asystole, as were different C:V ratios. Optimizing resuscitation is important to prevent morbidity and mortality from perinatal asphyxia. In this study metabolomics profiles were studied in newborn pigs that were asphyxiated and resuscitated using different protocols to identify biomarkers for subject characterization, intervention effects and possibly prognosis
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